Moss-derived human complement factor H modulates retinal immune response and attenuates retinal degeneration.

Area of Science:

• Ophthalmology
• Immunology
• Biotechnology

Background:

• Age-related macular degeneration (AMD) is a progressive retinal disease linked to complement system dysregulation and microglia activation.
• A specific genetic variant in complement factor H (CFH) significantly increases AMD risk.
• Moss-derived recombinant human CFH proteins (CPV-101, CPV-104) were investigated for their therapeutic potential in AMD.

Purpose of the Study:

• To evaluate the efficacy of moss-derived recombinant human CFH proteins (CPV-101 and CPV-104) in modulating microglia reactivity and limiting retinal degeneration in an AMD mouse model.
• To assess the impact of CFH substitution on complement activation and retinal cell responses.

Main Methods:

• Production of glycosylated, sialylated recombinant human CFH variants (CPV-101, CPV-104) in moss suspension cultures.
• Intravitreal injection of CFH variants into mice followed by light-induced retinal damage.
• Analysis of mononuclear phagocyte and Müller cell reactivity, gene expression, and retinal degeneration using various assays including immunostaining, qRT-PCR, OCT, BAF, and TUNEL staining.

Main Results:

• Treatment with moss-derived CFH proteins reduced complement activation and MAC deposition in the retina.
• CFH substitution ameliorated mononuclear phagocyte and Müller cell reactivity in light-exposed retinas.
• Moss-derived CFH treatment attenuated light-induced retinal degeneration in mice.

Conclusions:

• Moss-derived recombinant human CFH variants (CPV-101, CPV-104) effectively modulate the alternative complement pathway.
• These CFH proteins counteract gliosis and reduce light-induced retinal degeneration.
• This approach presents a promising therapeutic strategy for age-related macular degeneration.